Aims: 

Rapid spreading of the electrical impulse throughout the heart, ensured by electrical coupling at the gap junctions (GJs), is essential for synchronised contraction. Alterations in myocardial architecture and topology of GJs may result in conduction abnormalities facilitating occurrence of lethal arrhythmias. We examined ultrastructure and arrhythmia susceptibility of the hearts from various models of diseased rats.

Methods: 

Ventricular tissues of male, 12-16 week-old rats suffering from hypertension (spontaneous and L-NAME-induced), diabetes and hereditary hypertriglyceridaemia as well as age-matched controls were routinely processed for electron microscopic examination. Lethal arrhythmia susceptibility, i.e. incidence of electrically- or hypokalemia-induced ventricular fibrillation (VF) was monitored in isolated heart preparation.

Results: 

Marked subcellular alterations indicating hypertrophy of cardiomyocytes were found in both models of hypertensive while not in diabetic or hypertriglyceridaemic rat hearts. Extracellular matrix alteration, i.e. replacement fibrosis was pronounced in hearts of L-NAME and HTG and to lesser extent in diabetic rats. Unlike to control rat hearts with majority of GJs confined to intercalated disc (end-to-end type), diseased rat hearts were characterized by enhanced number of lateral (side-to-side-type) GJs. Lateralization was most pronounced in hypertensive and hypertriglyceridaemic, while much less in diabetic rat hearts. In correlation with structural and GJs changes, highest susceptibility to VF exhibited hypertensive and hypertriglyceridaemic rat hearts, while lower diabetic and lowest control rat hearts.

Conclusion: 

The findings support hypothesis that structural and gap junctions remodelling increase susceptibility of the heart to lethal arrhythmias.

Supported by APVV 51- 059505.